tbuckley/cabot-search huggingface dataset:
European Respiratory Society statement on familial pulmonary fibrosis
Authors: Raphael Borie, Caroline Kannengiesser, Katerina Antoniou, Francesco Bonella, Bruno Crestani, Aurélie Fabre, Antoine Froidure, Liam Galvin, Matthias Griese, Jan C. Grutters, Maria Molina-Molina, Venerino Poletti, Antje Prasse, Elisabetta Renzoni, Jasper van der Smagt, Coline H.M. van Moorsel
Journal: European Respiratory Journal (2022)

Genetic predisposition to pulmonary fibrosis has been confirmed by the discovery of several gene mutations that cause pulmonary fibrosis. Although genetic sequencing of familial pulmonary fibrosis (FPF) cases is embedded in routine clinical practice in several countries, many centres have yet to incorporate genetic sequencing within interstitial lung disease (ILD) services and proper international consensus has not yet been established. An international and multidisciplinary expert Task Force (pulmonologists, geneticists, paediatrician, pathologist, genetic counsellor, patient representative and librarian) reviewed the literature between 1945 and 2022, and reached consensus for all of the following questions: 1) Which patients may benefit from genetic sequencing and clinical counselling? 2) What is known of the natural history of FPF? 3) Which genes are usually tested? 4) What is the evidence for telomere length measurement? 5) What is the role of common genetic variants (polymorphisms) in the diagnostic workup? 6) What are the optimal treatment options for FPF? 7) Which family members are eligible for genetic sequencing? 8) Which clinical screening and follow-up parameters may be considered in family members? Through a robust review of the literature, the Task Force offers a statement on genetic sequencing, clinical management and screening of patients with FPF and their relatives. This proposal may serve as a basis for a prospective evaluation and future international recommendations.
Over-the-counter Dispensing: Widening Access to Inhaled Corticosteroid/Formoterol Reliever Therapy
Authors: Richard Beasley, Lee Hatter
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Over-the-Counter Dispensing: Widening Access to ICS/Formoterol Reliever Therapy ." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –
Reply: Association between triple therapy and major adverse cardiovascular events in COPD patients
Authors: Ming-Jin Yang, Shu-Liang Guo, Don D. Sin
Journal: European Respiratory Journal (2022)

<b>Long-acting bronchodilators should be used with caution in COPD patients with cardiovascular comorbidities or with a heightened risk of adverse cardiovascular events</b>https://bit.ly/3hxZzPk
Digital disparities among healthcare workers in typing speed between generations, genders, and medical specialties: cross sectional study
Authors: Alex R Schuurman, M E Baarsma, W Joost Wiersinga, Joppe W Hovius
Journal: BMJ (2022)

To investigate the typing skills of healthcare professionals.Cross sectional study.Two large tertiary medical centres in Amsterdam, the Netherlands.2690 hospital employees working in patient care, research, or medical education.Participants completed a custom built, web based, Santa themed, typing test in 60 seconds and filled out an associated questionnaire. The primary outcome was corrected typing speed, defined as crude typing speed (words per minute) multiplied by accuracy (correct characters as a percentage of total characters in the final transcribed text). Feelings towards administrative tasks scored on the Visual Analogue Scale to Weigh Respondents' Internalised Typing Enjoyment (VAS-WRITE), in which 0 represents the most negative and 100 the most positive feelings towards administration, were also recorded.Between 18 and 21 May 2021, a representative cohort of 2690 study participants was recruited (1942 (72.2%) were younger than 40 years; 2065 (76.8%) were women). Respondents' mean typing speed was 60.1 corrected words per minute (standard deviation 20.8; range 8.0-136.6) with substantial differences between professions and specialties, in which physicians in internal medicine were the fastest among the medical professionals. Typing speed decreased significantly with every age decade (rho -0.51, P<0.001), and people with a history of completing a typing course were more than 20% faster than those who had not (mean difference 12.1 words (standard error 0.8), (95% confidence interval 10.6 to 13.6), P<0.001). The corrected typing speed did not differ between genders (0.5 (0.9) words, (-1.4 to 2.4), P=0.61). Women were less negative towards administration than were men (mean difference VAS-WRITE score 7.68 (standard error 1.17), (95% confidence interval 5.33 to 10.03), P<0.001). Of all professional groups, medical staff reported the most negative feelings towards administration (mean VAS-WRITE score of 33.5 (standard deviation 22.9)).Important differences were reported in typing proficiency between age groups, professions, and medical specialties. Specific groups are at a disadvantage in an increasingly digitalised healthcare system, and these data could inform the implementation of training modules and alternative methods of data entry to level the playing field.
Venetoclax with decitabine versus decitabine monotherapy in elderly acute myeloid leukemia: a propensity score-matched analysis
Authors: Daehun Kwag, Byung-Sik Cho, Su-Yeon Bang, Jong Hyuk Lee, Gi-June Min, Sung-Soo Park, Silvia Park, Jae-Ho Yoon, Sung-Eun Lee, Ki-Seong Eom, Yoo-Jin Kim, Seok Lee, Chang-Ki Min, Seok-Goo Cho, Jong Wook Lee, Hee-Je Kim
Journal: Blood Cancer Journal (2022)

Abstract Venetoclax (VEN) combined with azacitidine (AZA) or decitabine (DEC) has been approved for older adults with acute myeloid leukemia (AML) unfit for intensive chemotherapy based on the pivotal VIALE-A trial. However, this trial only compared AZA + VEN with AZA monotherapy. Therefore, we compared the outcomes of consecutive older adults (65 years or older) with newly diagnosed AML who received DEC ( n = 230) or DEC + VEN ( n = 74) after propensity score matching to construct a one-to-one matched cohort by the nearest neighbor algorithm. The median overall survival was longer in the DEC + VEN group than in the DEC group (13.4 months vs. 8.3 months, p = 0.01). The median event-free survivals were 8.6 and 5.8 months in the DEC + VEN and DEC groups, respectively ( p = 0.02). The response rate (complete response, complete response with incomplete hematologic recovery, and morphologic leukemia-free state) was significantly higher in the DEC + VEN group than in the DEC group (70.3% vs. 24.3%, p &lt; 0.01). The 30-day (2.7% vs. 9.5%, p = 0.17) and 60-day (9.5% vs. 18.9%, p = 0.16) mortality rates did not differ between the two groups, nor did the median hospitalization and transfusion rates (hospitalization: 23 days vs. 21 days, p = 0.20; red blood cells: 3.2 units/month vs. 3.5 units/month, p = 0.73; platelets: 2.7 units/month vs. 2.3 units/months, p = 0.48). Of those who received DEC + VEN and became leukemia-free, 29% underwent allogeneic stem cell transplantation and had excellent survival outcomes (one-year survival: 79.4%; one-year non-relapse mortality: 13.3%). This study is the first to provide real-world evidence that DEC + VEN has superior outcomes to DEC monotherapy.
Surfactant Semiconductors as Trojan Horses in Cell‐Membranes for On‐Demand and Spatial Regulation of Oxidative Stress
Authors: Marian Jaschke, Masina Plenge, Marius Kunkel, Tina Lehrich, Julia Schmidt, Kilian Stöckemann, Dag Heinemann, Stephan Siroky, Anaclet Ngezahayo, Sebastian Polarz
Journal: Advanced Healthcare Materials (2022)

Abstract Oxidative stress is a cause for numerous diseases and aging processes. Thus, researchers are keen to tune the level of intracellular stress and to learn from that. An unusual approach is presented here. The methodology involves multifunctional surfactants. Although their molecular design is nonbiological—a fullerenol head group attached covalently to pi‐conjugated dyes—the surfactants possess superior biocompatibility. Using an intrinsic fluorescence signal as a probe, it is shown that the amphiphiles become incorporated into the Caco‐2 cells. There, they are able to exhibit additional functions. The compound reduces cellular stress in dark reaction pathways. The antagonistic property is activated under irradiation, the photocatalytic production of reactive oxygen species (ROS), resulting in cell damage. The feature is activated even by near‐infrared light (NIR‐light) via a two‐photon process. The properties as molecular semiconductors lead to a trojan horse situation and allows the programming of the spatial distribution of cytotoxicity.
Efficient preclinical treatment of cortical T cell acute lymphoblastic leukemia with T lymphocytes secreting anti-CD1a T cell engagers
Authors: Anaïs Jiménez-Reinoso, Néstor Tirado, Alba Martinez-Moreno, Víctor M Díaz, Marina García-Peydró, Oana Hangiu, Laura Díez-Alonso, Ángela Albitre, Petronila Penela, Maria L Toribio, Pablo Menéndez, Luis Álvarez-Vallina, Diego Sánchez Martínez
Journal: Journal for ImmunoTherapy of Cancer (2022)

The dismal clinical outcome of relapsed/refractory (R/R) T cell acute lymphoblastic leukemia (T-ALL) highlights the need for innovative targeted therapies. Although chimeric antigen receptor (CAR)-engineered T cells have revolutionized the treatment of B cell malignancies, their clinical implementation in T-ALL is in its infancy. CD1a represents a safe target for cortical T-ALL (coT-ALL) patients, and fratricide-resistant CD1a-directed CAR T cells have been preclinically validated as an immunotherapeutic strategy for R/R coT-ALL. Nonetheless, T-ALL relapses are commonly very aggressive and hyperleukocytic, posing a challenge to recover sufficient non-leukemic effector T cells from leukapheresis in R/R T-ALL patients.We carried out a comprehensive study using robust in vitro and in vivo assays comparing the efficacy of engineered T cells either expressing a second-generation CD1a-CAR or secreting CD1a x CD3 T cell-engaging Antibodies (CD1a-STAb).We show that CD1a-T cell engagers bind to cell surface expressed CD1a and CD3 and induce specific T cell activation. Recruitment of bystander T cells endows CD1a-STAbs with an enhanced in vitro cytotoxicity than CD1a-CAR T cells at lower effector:target ratios. CD1a-STAb T cells are as effective as CD1a-CAR T cells in cutting-edge in vivo T-ALL patient-derived xenograft models.Our data suggest that CD1a-STAb T cells could be an alternative to CD1a-CAR T cells in coT-ALL patients with aggressive and hyperleukocytic relapses with limited numbers of non-leukemic effector T cells.
‘You give me fever!’: are health services ready for immune cell engager therapy in advanced solid malignancies?
Authors: Claire Pettinger, Claire Livings, Rafael Grochot, Andrew Furness, Juanita Lopez
Journal: Journal for ImmunoTherapy of Cancer (2022)

Immune cell engager therapeutic strategies using bioengineered molecules to redirect immune cells into tumor are starting to demonstrate promising clinical activity in multiple early phase trials across numerous targets and a range of solid tumor types. These therapies, however, carry the risk of exaggerated cytokine-mediated on-target off-tumor adverse events that require highly specialized inpatient facilities. We report here the Royal Marsden experience of treating patients with advanced solid tumors on early phase immune engager clinical trials in a dedicated inpatient facility, focusing specifically on patterns of cytokine-mediated toxicity seen and proposing a risk-mitigation algorithm for the safe, feasible and scalable delivery of these therapies.
Multifunctionalized carbon-fiber-reinforced polyetheretherketone implant for rapid osseointegration under infected environment
Authors: Xiao Wang, Lisha Pan, Ao Zheng, Lingyan Cao, Jin Wen, Tingshu Su, Xiangkai Zhang, Qingfeng Huang, Xinquan Jiang
Journal: Bioactive Materials (2022)

Carbon fiber reinforced polyetheretherketone (CFRPEEK) possesses a similar elastic modulus to that of human cortical bone and is considered as a promising candidate to replace metallic implants. However, the bioinertness and deficiency of antibacterial activities impede its application in orthopedic and dentistry. In this work, titanium plasma immersion ion implantation (Ti-PIII) is applied to modify CFRPEEK, achieving unique multi-hierarchical nanostructures and active sites on the surface. Then, hybrid polydopamine (PDA)@ZnO-EDN1 nanoparticles (NPs) are introduced to construct versatile surfaces with improved osteogenic and angiogenic properties and excellent antibacterial properties. Our study established that the modified CFRPEEK presented favorable stability and cytocompatibility. Compared with bare CFRPEEK, improved osteogenic differentiation of rat mesenchymal stem cells (BMSCs) and vascularization of human umbilical vein endothelial cells (HUVECs) are found on the functionalized surface due to the zinc ions and EDN1 releasing. In vitro bacteriostasis assay confirms that hybrid PDA@ZnO NPs on the functionalized surface provided an effective antibacterial effect. Moreover, the rat infected model corroborates the enhanced antibiosis and osteointegration of the functionalized CFRPEEK. Our findings indicate that the multilevel nanostructured PDA@ZnO-EDN1 coated CFRPEEK with enhanced antibacterial, angiogenic, and osteogenic capacity has great potential as an orthopedic/dental implant material for clinical application.
Aetiology, clinical features, diagnostic studies, and outcomes of community-acquired pneumonia in kidney transplant recipients admitted to hospital: a multicentre retrospective French cohort study
Authors: Benoît Schwartz, Vincent Dupont, Sandra Dury, Aline Carsin-Vu, None Thomas Guillard, Sophie Caillard, Luc Frimat, Stephane Sanchez, Betoul Schvartz, Firouzé Bani-Sadr, None Damien Jolly, None Philippe Rieu, None Antoine Goury
Journal: Clinical Microbiology and Infection (2022)

To assess the aetiology, clinical features, diagnostic studies and outcomes of community-acquired pneumonia (CAP) in a French cohort of hospitalized kidney transplant recipients.We performed a retrospective, multicentre study in kidney transplant recipients admitted to ten French centres for CAP from January 2016 to December 2018. CAP discharge diagnoses were clinically and radiologically validated. We assessed a descriptive analysis of all confirmed CAP including medical ward and intensive care unit admissions.One hundred sixty-five CAP episodes in 132 patients were included. Median time from transplantation to admission was 6.4 (interquartile range, 1.6-12.3) years, with corticosteroid exposure in 112/165 (67.9%) cases. Sputum culture was performed in 47/165 (28.5%) cases including 7/47 (14.9%) positive samples. Bronchoscopy was performed in 87/165 (52.7%) cases with pathogens identified in 39/87 (44.8%) cases. Microbiological studies led to identifying a respiratory pathogen in 64/165 (38.8%) CAP episodes including 11/64 (17.2%) polymicrobial cases. Among these 64 episodes, 75 microorganisms were identified; 46/75 (61.3%) were core respiratory pathogens and 29/75 (38.7%) were opportunistic or drug-resistant organisms including Pneumocystis jirovecii 9/75 (12%), Pseudomonas aeruginosa 5/75 (6.7%), multidrug-resistant Enterobacteriaceae 4/75 (5.3%), and Aspergillus 4/75 (5.3%). Patients required intensive care unit admission in 26/165 (15.8%) episodes, invasive ventilation in 20/165 (12.1%) cases, and 22/165 (13.3%) needed in-hospital dialysis.CAP episodes occurred in kidney transplant recipients with a long history of immunosuppressive drug exposure. Diagnostic studies identified a microorganism in more than one-third of CAP episodes, including drug-resistant and opportunistic pathogens.
A Polymer Canvas with the Stiffness of the Bone Matrix to Study and Control Mesenchymal Stem Cell Response
Authors: Alessandra Zanut, Rui Li, Ru Deng, Xiangyu Liu, Martin Rejhon, Weiqiang Chen, Marcus Weck, Giuseppe Maria de Peppo, Elisa Riedo
Journal: Advanced Healthcare Materials (2022)

Abstract Reproducing in vitro the complex multiscale physical features of human tissues creates novel biomedical opportunities and fundamental understanding of cell−environment interfaces and interactions. While stiffness has been recognized as a key driver of cell behavior, systematic studies on the role of stiffness have been limited to values in the KPa−MPa range, significantly below the stiffness of bone. Here, a platform enabling the tuning of the stiffness of a biocompatible polymeric interface up to values characteristic of human bone is reported, which are in the GPa range, by using extremely thin polymer films on glass and cross‐linking the films using ultraviolet (UV) light irradiation. It is shown that a higher stiffness is related to better adhesion, proliferation, and osteogenic differentiation, and that it is possible to switch on/off cell attachment and growth by solely tuning the stiffness of the interface, without any surface chemistry or topography modification. Since the stiffness is tuned directly by UV irradiation, this platform is ideal for rapid and simple fabrication of stiffness patterns and gradients, thus representing an innovative tool for combinatorial studies of the synergistic effect of tissue environmental cues on cell behavior, and creates new opportunities for next‐generation biosensors, single‐cell patterning, and lab‐on‐a‐chip devices.
Clear‐Box Machine Learning for Virtual Screening of 2D Nanozymes to Target Tumor Hydrogen Peroxide
Authors: Xuejiao J. Gao, Jun Yan, Jia‐Jia Zheng, Shengliang Zhong, Xingfa Gao
Journal: Advanced Healthcare Materials (2022)

Targeting tumor hydrogen peroxide (H2 O2 ) with catalytic materials has provided a novel chemotherapy strategy against solid tumors. Because numerous materials have been fabricated so far, there is an urgent need for an efficient in silico method, which can automatically screen out appropriate candidates from materials libraries for further therapeutic evaluation. In this work, adsorption-energy-based descriptors and criteria are developed for the catalase-like activities of materials surfaces. The result enables a comprehensive prediction of H2 O2 -targeted catalytic activities of materials by density functional theory (DFT) calculations. To expedite the prediction, machine learning models, which efficiently calculate the adsorption energies for 2D materials without DFT, are further developed. The finally obtained method takes advantage of both interpretability of physics model and high efficiency of machine learning. It provides an efficient approach for in silico screening of 2D materials toward tumor catalytic therapy, and it will greatly promote the development of catalytic nanomaterials for medical applications.
Corrigendum to ‘The burden of respiratory syncytial virus in children under 5 years of age in Norway’ [Journal of Infection Volume 84, Issue 2 (2022) Pages 205-215]
Authors: Lise Beier Havdal, Håkon Bøås, Terese Bekkevold, Anne-Marte Bakken Kran, Astrid Elisabeth Rojahn, Ketil Størdal, Sara Debes, Henrik Døllner, Svein Arne Nordbø, Bjørn Barstad, Elisebet Haarr, Liliana Vázquez Fernández, Britt Nakstad, Christopher Inchley, Elmira Flem
Journal: Journal of Infection (2022)
Pulmonary Langerhans-Cell Histiocytosis
Authors: Rami Qanneta, Antoni Raventos-Estelle
Journal: New England Journal of Medicine (2022)

A 40-year-old man with a history of smoking and a 2-week history of cough, dyspnea, night sweats, and pleuritic chest pain was found to have a pneumothorax. A chest CT showed multiple cysts and nodules.
Common kinase mutations do not impact optimal molecular responses in core binding factor acute myeloid leukemia treated with fludarabine, cytarabine, and <scp>G‐CSF</scp> based regimens
Authors: Jayastu Senapati, Tareq Abuasab, Fadi G. Haddad, Farhad Ravandi, Tapan Kadia, Courtney DiNardo, Naval Daver, Naveen Pemmaraju, Yesid Alvarado, Mark A. Brandt, Hagop Kantarjian, Gautam Borthakur
Journal: American Journal of Hematology (2022)

Common kinase mutations do not impact optimal molecular responses in core binding factor acute myeloid leukemia treated with fludarabine, cytarabine, and G-CSF based regimensTo the Editor:Core binding factor (CBF) acute myeloid leukemia (AML), defined by the cytogenetic abnormalities t(8;21)(q22;q22) and inversion(16)(p13; q22)/t(16;16)(p13;q22) chromosomal changes, is considered a favorable risk AML, with an estimated 5-year overall survival (OS) rate of ≈70%. 1,25][6] Two variables, one at baseline and one on treatment can prognosticate outcomes in CBF-AML.The first is the presence of concurrent kinase pathway mutations (KIT, RAS, FLT3) that negatively affect survival outcomes, 7,8 particularly relapse.The second is the ability to precisely assess measurable residual disease (MRD) using quantitative polymerase chain reaction (PCR) for unique fusion transcripts.This aids in the
A genetically engineered, stem-cell-derived cellular vaccine
Authors: Amanda Cooper, Adam Sidaway, Abishek Chandrashekar, Elizabeth Latta, Krishnendu Chakraborty, Jingyou Yu, Katherine McMahan, Victoria Giffin, Cordelia Manickam, Kyle Kroll, Matthew Mosher, R. Keith Reeves, Rihab Gam, Elisa Arthofer, Modassir Choudhry, Tom Henley, Dan H. Barouch
Journal: Cell Reports Medicine (2022)

Despite rapid clinical translation of COVID-19 vaccines in response to the global pandemic, an opportunity remains for vaccine technology innovation to address current limitations and meet challenges of inevitable future pandemics. We describe a universal vaccine cell (UVC) genetically engineered to mimic natural physiological immunity induced upon viral infection of host cells. Cells engineered to express the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike as a representative viral antigen induce robust neutralizing antibodies in immunized non-human primates. Similar titers generated in this established non-human primate (NHP) model have translated into protective human neutralizing antibody levels in SARS-CoV-2-vaccinated individuals. Animals vaccinated with ancestral spike antigens and subsequently challenged with SARS-CoV-2 Delta variant in a heterologous challenge have an approximately 3 log decrease in viral subgenomic RNA in the lungs. This cellular vaccine is designed as a scalable cell line with a modular poly-antigenic payload, allowing for rapid, large-scale clinical manufacturing and use in an evolving viral variant environment.
Remote Ischemic Conditioning vs Usual Care and Neurologic Function in Acute Moderate Ischemic Stroke
Authors: Fernando Pico, Julien Labreuche, Pierre Amarenco
Journal: JAMA (2022)

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